[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT03670966":3,"trial-entities:NCT03670966":229,"trial-summary:NCT03670966":237},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":31,"study_type":35,"primary_purpose":36,"phases":37,"enrollment_info":40,"interventions":43,"primary_outcomes":132,"secondary_outcomes":137,"sex":160,"minimum_age":161,"maximum_age":162,"healthy_volunteers":163,"eligibility_criteria":164,"std_ages":202,"locations":205,"central_contacts":223,"overall_officials":225,"references":227,"see_also_links":228},"NCT03670966","RG1003349","211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome","A Phase I\u002FII Study Evaluating Escalating Doses of 211At-Labeled Anti-CD45 MAb BC8-B10 (211At-BC8-B10) Followed by Related Haplo-Identical Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Leukemia or Myelodysplastic Syndrome (MDS)","RECRUITING","2029-10-20","2026-06","2026-06-22","2019-07-10","Fred Hutchinson Cancer Center","OTHER",true,"This phase I\u002FII trial studies the side effects and best dose of a radioactive agent linked to an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after a transplant may stop this from happening.","OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody BC8-B10.\n\nPREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine intravenously (IV) over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Patients also undergo TBI on day -1.\n\nTRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant on day 0.\n\nGVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or PO three times daily (TID) on days 5-35, and tacrolimus IV over 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per physician discretion. Patients also begin granulocyte colony-stimulating factor (G-CSF) IV or subcutaneously (SC) on day 5 to continue until absolute neutrophil count (ANC) \\> 1000\u002Fmm\\^3 x 3 days.\n\nPatients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.\n\nAfter completion of study treatment, patients are followed up at day 100, and at 6, 9, 12, 18, and 24 months.",[19,20,21,22,23,24,25,26,27,28,29,30],"Acute Lymphoblastic Leukemia in Remission","Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome","Acute Myeloid Leukemia in Remission","Chronic Myelomonocytic Leukemia","Myelodysplastic Syndrome With Excess Blasts","Recurrent Acute Lymphoblastic Leukemia","Recurrent Acute Myeloid Leukemia","Refractory Acute Lymphoblastic Leukemia","Refractory Acute Myeloid Leukemia","Recurrent Mixed Phenotype Acute Leukemia","Refractory Mixed Phenotype Acute Leukemia","Hematopoietic and Lymphoid Cell Neoplasm",[32,33,34],"Lymphoid Leukemia","Myeloid and Monocytic Leukemia","Other Hematopoietic","INTERVENTIONAL","TREATMENT",[38,39],"PHASE1","PHASE2",{"count":41,"type":42},30,"ESTIMATED",[44,53,63,74,81,88,96,104,113,122,126],{"type":45,"name":46,"description":47,"armGroupLabels":48,"otherNames":50},"BIOLOGICAL","Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10","Given via infusion",[49],"Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)",[51,52],"At 211 MAb BC8-B10","APAMISTAMAB-B10-ASTATINE AT-211",{"type":54,"name":55,"description":56,"armGroupLabels":57,"otherNames":58},"DRUG","Cyclophosphamide","Given IV",[49],[59,60,61,62],"(-)-Cyclophosphamide","Asta B 518","B-518","WR-138719",{"type":64,"name":65,"description":66,"armGroupLabels":67,"otherNames":68},"RADIATION","Total-Body Irradiation","Undergo TBI",[49],[69,70,71,72,73],"Total Body Irradiation","SCT_TBI","Whole Body Irradiation","Whole-Body Irradiation","TBI",{"type":75,"name":76,"description":77,"armGroupLabels":78,"otherNames":79},"PROCEDURE","Peripheral Blood Stem Cell Transplantation","Undergo PBSC transplantation",[49],[80],"PBPC transplantation",{"type":75,"name":82,"description":83,"armGroupLabels":84,"otherNames":85},"Bone Marrow Transplantation","Undergo bone marrow transplant",[49],[86,87],"Bone Marrow Grafting","BMT",{"type":54,"name":89,"description":90,"armGroupLabels":91,"otherNames":92},"Mycophenolate Mofetil","Given IV or PO",[49],[93,94,95],"115007-34-6","MMF","Cellcept",{"type":45,"name":97,"description":98,"armGroupLabels":99,"otherNames":100},"Recombinant Granulocyte Colony-Stimulating Factor","Given IV or SC",[49],[101,102,103],"143011-72-7","Recombinant Colony-Stimulating Factor 3","rhG-CSF",{"type":54,"name":105,"description":56,"armGroupLabels":106,"otherNames":107},"Fludarabine Phosphate",[49],[108,109,110,111,112],"2-F-ara-AMP","Beneflur","Fludara","Fludarabine-5''-Monophosphate","SH T 586",{"type":54,"name":114,"description":90,"armGroupLabels":115,"otherNames":116},"Tacrolimus",[49],[117,118,119,120,121],"Prograf","Protopic","FK 506","FK-506","Tacforius",{"type":75,"name":123,"description":124,"armGroupLabels":125},"Bone Marrow Aspiration and Biopsy","Undergo bone marrow biopsy and aspiration",[49],{"type":75,"name":127,"description":128,"armGroupLabels":129,"otherNames":130},"Biospecimen Collection","Undergo blood sample collection",[49],[131],"Biological Sample Collection",[133],{"measure":134,"description":135,"timeFrame":136},"Incidence of dose limiting toxicity (DLT)","DLT is defined as a grade III\u002FIV regimen-related toxicity (Bearman scale). The maximum tolerated dose will be defined as the dose of 211\\^At-BC8-B10 used in combination with the reduced-intensity hematopoietic cell transplantation conditioning regimen that is associated with a grade III\u002FIV regimen-related toxicity or true DLT rate of 25%. The data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels visited. Based on this fitted model, the maximum tolerated dose is estimated to be the dose that is associated with a toxicity rate of 25%.","Up to 30 days post-transplant, with a review period for occurrence of veno-occlusive disease (VOD)\u002Fsinusoidal obstruction syndrome (SOS) extended to 60 days post-transplant",[138,141,143,146,148,150,152,154,157],{"measure":139,"timeFrame":140},"Achievement of remission","Up to 2 years",{"measure":142,"timeFrame":140},"Rate of engraftment",{"measure":144,"timeFrame":145},"Donor chimerism","At days 28, 56, 84, 180, and at 1 year",{"measure":147,"timeFrame":140},"Non-relapse mortality (NRM)",{"measure":149,"timeFrame":140},"Number of patients experiencing Immune reconstitution",{"measure":151,"timeFrame":140},"Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD)",{"measure":153,"timeFrame":140},"Number of patients experiencing Moderate\u002Fsevere chronic GVHD",{"measure":155,"timeFrame":156},"Overall survival","Up to 100 days",{"measure":158,"timeFrame":159},"Disease-free survival","Up to day 100","ALL","18 Years","75 Years",false,{"inclusion":165,"exclusion":187,"raw_text":201},[166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186],"Patients must have AML, ALL, high-risk MDS, or MPAL (also known as biphenotypic) meeting one of the following descriptions:","AML, ALL, or MPAL in first remission with evidence of measurable residual disease (MRD) by flow cytometry;","AML, ALL, or MPAL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen);","AML, ALL, or MPAL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens);","AML evolved from myelodysplastic or myeloproliferative syndromes;","MDS expressed as refractory anemia with excess blasts (RAEB)","Chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria.","Patients not in remission must have CD45-expressing leukemic blasts. Patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up \\>= 95% of nucleated cells in the marrow).","Patients must be \\>= 18 and =\\\u003C 75 years of age.","Patients should have a circulating blast count of less than 10,000\u002Fmm\\^3 (control with hydroxyurea or similar agent is allowed).","Patients must have an estimated creatinine clearance greater than 50\u002Fml per minute by the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 days prior to registration.","Total bilirubin within normal limits","Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 2 times the upper limit of normal.","Eastern Cooperative Oncology Group (ECOG) \\\u003C 2 or Karnofsky \\>= 70.","Patients must be free of uncontrolled infection.","Patients with prior non-myeloablative or reduced-intensity conditioning allogeneic-HCT must have no evidence of ongoing GVHD and be off all immunosuppression for at least 6 weeks at time of enrollment.","Patients must have normal elastography.","If ferritin is elevated, patient must have less than 7 mg\u002Fg liver iron concentration on liver T2 magnetic resonance imaging (MRI).","Patients should have an official gastrointestinal (GI) consult prior to the transplant for full evaluation.","Patients must have a related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches.","DONOR: Donors must meet HLA matching criteria as well as standard Seattle Cancer Care Alliance (SCCA) criteria for PBSC or bone marrow donation. Preference should be given to donors who are mismatched at the HLA-A, -B and -DRB1 loci.",[188,189,190,191,192,193,194,195,196,197,198,199,200],"Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects.","Left ventricular ejection fraction \\\u003C 45%.","Corrected diffusion capacity of the lung for carbon monoxide (DLCO) \\\u003C 35% or receiving supplemental continuous oxygen. When pulmonary function tests (PFTs) cannot be obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of \\\u003C 89% during a 6MWT will be excluded","Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.","Patients who are known to be seropositive for human immunodeficiency virus (HIV).","Perceived inability to tolerate diagnostic or therapeutic procedures.","Active central nervous system (CNS) leukemia at time of treatment.","Patients with prior myeloablative allogeneic-HCT.","Women of childbearing potential who are pregnant (beta human chorionic gonadotropin \\[B-HCG\\]+) or breast feeding.","Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant.","Inability to understand or give an informed consent.","Allergy to murine-based monoclonal antibodies.","Known contraindications to radiotherapy.","Inclusion Criteria:\n\n* Patients must have AML, ALL, high-risk MDS, or MPAL (also known as biphenotypic) meeting one of the following descriptions:\n\n  * AML, ALL, or MPAL in first remission with evidence of measurable residual disease (MRD) by flow cytometry;\n  * AML, ALL, or MPAL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen);\n  * AML, ALL, or MPAL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens);\n  * AML evolved from myelodysplastic or myeloproliferative syndromes;\n  * MDS expressed as refractory anemia with excess blasts (RAEB)\n  * Chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria.\n* Patients not in remission must have CD45-expressing leukemic blasts. Patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up \\>= 95% of nucleated cells in the marrow).\n* Patients must be \\>= 18 and =\\\u003C 75 years of age.\n* Patients should have a circulating blast count of less than 10,000\u002Fmm\\^3 (control with hydroxyurea or similar agent is allowed).\n* Patients must have an estimated creatinine clearance greater than 50\u002Fml per minute by the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 days prior to registration.\n* Total bilirubin within normal limits\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 2 times the upper limit of normal.\n* Eastern Cooperative Oncology Group (ECOG) \\\u003C 2 or Karnofsky \\>= 70.\n* Patients must be free of uncontrolled infection.\n* Patients with prior non-myeloablative or reduced-intensity conditioning allogeneic-HCT must have no evidence of ongoing GVHD and be off all immunosuppression for at least 6 weeks at time of enrollment.\n* Patients must have normal elastography.\n* If ferritin is elevated, patient must have less than 7 mg\u002Fg liver iron concentration on liver T2 magnetic resonance imaging (MRI).\n* Patients should have an official gastrointestinal (GI) consult prior to the transplant for full evaluation.\n* Patients must have a related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches.\n* DONOR: Donors must meet HLA matching criteria as well as standard Seattle Cancer Care Alliance (SCCA) criteria for PBSC or bone marrow donation. Preference should be given to donors who are mismatched at the HLA-A, -B and -DRB1 loci.\n\nExclusion Criteria:\n\n* Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects.\n* Left ventricular ejection fraction \\\u003C 45%.\n* Corrected diffusion capacity of the lung for carbon monoxide (DLCO) \\\u003C 35% or receiving supplemental continuous oxygen. When pulmonary function tests (PFTs) cannot be obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of \\\u003C 89% during a 6MWT will be excluded\n* Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.\n* Patients who are known to be seropositive for human immunodeficiency virus (HIV).\n* Perceived inability to tolerate diagnostic or therapeutic procedures.\n* Active central nervous system (CNS) leukemia at time of treatment.\n* Patients with prior myeloablative allogeneic-HCT.\n* Women of childbearing potential who are pregnant (beta human chorionic gonadotropin \\[B-HCG\\]+) or breast feeding.\n* Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant.\n* Inability to understand or give an informed consent.\n* Allergy to murine-based monoclonal antibodies.\n* Known contraindications to radiotherapy.",[203,204],"ADULT","OLDER_ADULT",[206],{"facility":207,"status":8,"city":208,"state":209,"zip":210,"country":211,"contacts":212,"geoPoint":220},"Fred Hutch\u002FUniversity of Washington Cancer Consortium","Seattle","Washington","98109","United States",[213,218],{"name":214,"role":215,"phone":216,"email":217},"Phuong Vo","CONTACT","206-667-2749","ptvo@fredhutch.org",{"name":214,"role":219},"PRINCIPAL_INVESTIGATOR",{"lat":221,"lon":222},47.60621,-122.33207,[224],{"name":214,"role":215,"phone":216,"email":217},[226],{"name":214,"affiliation":13,"role":219},[],[],{"nct_id":4,"conditions":230,"biomarkers":235},[231,232,22,233,234],"Acute Lymphoblastic Leukemia","Acute Myeloid Leukemia","Mixed Phenotype Acute Leukemia","Myelodysplastic Syndrome",[236],"PTPRC Gene",{"nct_id":4,"found":15,"summary":238,"prompt_version":248},{"design":239,"status":240,"heading":241,"summary":242,"follow_up":243,"word_count":244,"commitments":245,"compensation":246,"drugs_mentioned":247},"This is a dose-escalation study involving approximately 30 participants. It is an interventional study, meaning participants will receive specific treatments.","completed","Study of 211At-BC8-B10 and Stem Cell Transplant for High-Risk Leukemia or MDS","This study is looking at the side effects and best dose of a treatment called 211At-BC8-B10, which is a radioactive agent attached to an antibody. This treatment is given before a donor stem cell transplant for people with high-risk acute leukemia or myelodysplastic syndrome (MDS) that has returned or isn't responding to other treatments. 211At-BC8-B10 is designed to target and interfere with cancer cells. Before the transplant, you would also receive chemotherapy (fludarabine and cyclophosphamide) and total body irradiation to prepare your body. The main goal is to see how safe the 211At-BC8-B10 treatment is, especially looking for serious side effects like veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) within 30 to 60 days after transplant. This study is for adults aged 18 to 75 with specific types of leukemia or MDS.","After treatment, you would have follow-up visits at day 100, and at 6, 9, 12, 18, and 24 months.",133,"You would receive an infusion of 211At-BC8-B10, chemotherapy, and total body irradiation, followed by a stem cell transplant. You would also have blood draws and bone marrow biopsies throughout the study.","Not stated in the trial record.",[55],"v2"]